Galapagos (Croatia)

In this paper we deal with a not well known orthopteran species described from Croatia--Krauss' bush-cricket, Platycleis kraussi Padewieth, 1900 with unknown type series. After systematic field studies the species was found only three kilometres from Padewieth's locus typicus, in Francikovac near Senj (Croatia). It was found to be the same as Bicolorana kuntzeni (Ramme, 1931), thus B. kuntzeni (Ramme, 1931) syn. nov. became a synonym of Bicolorana kraussi (Padewieth, 1900) comb. nov. which is moved into genus Bicolorana Zeuner, 1941. Since the type was lost a neotype of B. kraussi is designated and deposited in the Naturalis Biodiversity Center (Leiden, the Netherlands). Historical review of this species' taxonomy is given. An improved description is presented showing some variability of certain morphological characters. The morphology, morphometrics and bioacoustic data of the species are compared with those of the closely related B. bicolor (Philippi, 1830) and Modestana modesta (Fieber, 1853). Vichetia helleri syn. nov. is regarded a synonym of Bicolorana bicolor. The literature and new distribution data are gathered and presented.

Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coli DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coli DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coli topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and ΔtolC E. coli strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

A review of the Croatian and Serbian Tetrigidae is given and first records of Tetrix undulata (Sowerby, 1806) for Croatia and Serbia as well as Tetrix tuerki (Krauss, 1876) and Tetrix transsylvanica (Bazyluk & Kis, 1960) comb. nov. for Croatia are presented. The status of the genus Uvarovitettix Bazyluk & Kis, 1960 and the taxonomic position of T. transsylvanica comb. nov. are discussed. The genus Uvarovitettix Bazyluk & Kis, 1960 syn. nov. is synonymised with the genus Tetrix Latreille, 1802. A new subspecies from Croatia and Slovenia, Tetrix transsylvanica hypsocorypha Skejo, 2014 subspecies nova, is described. Tetrix pseudodepressa (Ingrisch, 2006) comb. nov. and Tetrix depressa (Brisout de Barneville, 1848) comb. nov. are moved to the genus Tetrix and the genus Depressotetrix Karaman, 1960 syn. nov. is synonymised with the genus Tetrix. Tetrix gibberosa (Wang & Zheng, 1993) inc. sed. and T. nodulosa (Fieber, 1853) inc. sed. are now considered to be species of uncertain placement within the genus Tetrix. New combination is also given to Paratettix tuberculata (Zheng & Jiang, 1997), primarily placed within the genus Mishtshenkotetrix: Tetrix tuberculata (Zheng & Jiang, 1997) comb. nov., but its placement within the genus Tetrix is also uncertain.

Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX) in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN) assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA) levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

In vitro high-throughput screening was carried out in order to detect new activities for old drugs and to select compounds for the drug development process comprising new indications. Tebrophen, a known antiviral drug, was found to inhibit activities on inflammation and cancer related targets. In primary screening this semisynthetic halogenated polyphenol was identified to inhibit the activities of kinases ZAP-70 and Lck (IC50 0.34 µM and 16 µM, respectively), as well as hydrolase DPPIV (at 80 µM 41% inhibition). Next, it showed no cytotoxic effects on standard cell lines within 24 h. However, tebrophen slowed propagation of breast cancer (MDA-MB-231), osteosarcoma (U2OS) and cervical carcinoma (HeLa), through at least 35 population doublings in a dose-dependent manner. It completely stopped the division of the prostate cancer (PC3) cell line at 50 µM concentration and the cells entered massive cell death in less than 20 days. On the other hand, tebrophen did not influence the growth of normal fibroblasts. According to the measured oxidative burst and estimated in silico parameters its direct antioxidative ability is limited. The obtained results indicate that tebrophen can be considered a promising lead molecule for generating more soluble derivatives with specific anticancer efficacy.

Tryptophol is an aromatic alcohol and secondary metabolite of the opportunistic fungus Candida albicans. Although its toxicity profile at cell level has been poorly investigated, recent data point to cytotoxic, cytostatic, and genotoxic effects in lymphocytes and the induction of apoptosis in leukaemic blood monocytes. In this pilot study we evaluated the genotoxicity of tryptophol in vitro on four permanent cell lines of animal and human origin: ovary cells, alveolar epithelium, liver cells, and blood monocytes using the alkaline comet assay. We selected cells that might be principal targets of tryptophol and other low-molecular geno(toxins) secreted by Candida albicans during host invasion. Our results suggest that tryptophol applied in vitro at 2 mmol L(-1) for 24 h damages DNA in HepG2, A549 and THP-1 cells, obviously due to bioactivation and/or decomposition of the parent compound, which results in the formation of more genotoxic compound(s) and production of reactive species that additionally damage DNA. On the other hand, notably lower levels of primary DNA damage were recorded in CHO cells, which lack metabolic activity. Future studies with tryptophol should look further into mechanisms involved in its toxic action and should focus on other cell types prone to infection with Candida spp. such as vaginal epithelial cells or keratinocytes of human origin.